Interest in photoreleasable protecting groups (PRPGs) has expanded in recent years as it has become clear that his technology can be applied to a variety of endeavors including, multi-step organic synthesis (Greene, T. W. and Wuts, P. G. M., Protective Groups in Organic Synthesis, Wiley, New York, N.Y. (1991), p. 473; Pillai, V. N. R., Synthesis:1-26 (1980)), time resolved x-ray crystallography (Schlichiting et al., Nature 345:309-315 (1990)), photolithographic fabrication of DNA chips (Lockhart et al., Nature Biotechnol. 14:1675-1680 (1996); Pirrung, M. C., Chem. Rev. 97:473-488 (1997); Fodor et al.,Science (Washington, D.C.) 251:767-773 (1991); Pirrung et al., J. Org. Chem. 63:241-246 (1998)), photoregulation of proteins and cellular signaling pathways (Curley, K. and Lawrence, D.S., J. Am. Chem. Soc. 120:8573-8574 (1998); Wood et al., J. Am. Chem. Soc. 120:7145-7146 (1998); Pollit, S. K. and Schultz, P. G., Angew. Chem. Int. Ed. Engl. 37:2104-2107 (1998); Porter, et al., in Biological Applications of Photochemical Switches, H. Morrison, ed.; Wiley, New York, N.Y. (1993), pp. 197-242) and studies of ion channel dynamics in whole cells (Hess, G. P. and Grewer, C., Methods in Enzymology 291:443-473 (1998); Gee et al., J. Org. Chem. 61:1228-1233 (1996); Rossi et al., J. Biol. Chem. 272:32933-32939 (1997)). There are a number of established strategies for masking and photolytically releasing various functionalities. PRPGs based on derivatives of the ortho-nitrobenzyl group are perhaps the most widely used (Ottl et al., Bioconjugate Chem. 9:143-151 (1998); McCray et al., Proc. Natl. Acad, Sci. USA 77:7273-7241 (1980); Gee et al., J. Org. Chem. 60:4260-4263 (1995); Cameron, J. F. and Frechet, J. J. M., J. Am. Chem. Soc. 113:4303-4313 (1991)). More recent investigations have identified the xcex1-benzoin group and its derivatives as an alternative strategy (Peach et al., Tetrahedron 51:10013-10024 (1995); Pirrung et al., J. Org Chem. 63:241-246 (1998); Pirrung, M. C. and Bradley, J., J. Org. Chem. 60:1116-1117 (1995); Sheehan, J. C. and Wilson, R. M., J. Am. Chem. Soc. 86:5277-5281 (1964); Rock, R S. and Chan, S. I., J. Am. Chem. Soc. 120:10766-10767 (1998); Cameron et al., J. Chem. Soc. Chem. Commun. 923-924 (1995)). The latter releases the target functionality more rapidly following absorption of the photon and gives by-products that are generally more inert than those from the ortho-nitrobenzyl family. Lately, Givens, et al. (Givens et al., J. Am. Chem. Soc. 119:8369-8370(1997); Gee et al., J. Org. Chem. 61:1228-1233 (1996))have demonstrated the utility of the 4-hydroxyphenacyl group. One problem that remains in this area is control of the wavelengths required for functional group release. Most of the currently available technologies utilize wavelengths in the UV-B region of the spectrum, limiting their applicability in situations where the target molecule or other species in the matrix absorb in the same spectral region.
In a series of recent papers (Banerjee et al., Tetrahedron Lett. 39:4635-4638 (1998); Banejee, A. and Falvey, D. E., J. Am. Chem. Soc. 120:2965-2966 (1998); Banerjee, A. and Falvey, D. E., J. Org Chem. 62:6245-6251 (1997)), a modular approach to the design of PRPGs was advanced whereby the light absorption step is controlled by one element (an antenna or a sensitizer) and the bond scission step leading to release of the target molecule is controlled by a separate element (release group). In principle, such a strategy permits separate optimization of the wavelengths of light required for release and the rates and efficiencies of the bond scission process. This concept has been experimentally realized through the release of carboxylic acids from phenacyl esters 1a (infra) (Banerjee, A. and Falvey, D. E., J. Org. Chem. 62:6245-6251 (1997)). In this case the phenacyl group acts as the release group and the light absorption step is controlled by a separate molecule which functions as an electron donating sensitizer. The initial photochemical step is transfer of an electron from the excited sensitizer to the phenacyl group, generating a phenacyl anion radical 2. The latter rapidly eliminates a carboxylate anion. It was demonstrated that a variety of carboxylic acids could be released using this strategy.
The invention relates to the electron transfer mediated photochemical release of alcohols, phosphates and diacids. The alcohols are protected as mixed heteroarylacyl and arylacyl carbonate esters. Irradiation of mixtures containing electron donating sensitizers and the carbonate esters initiates a series of bond scission reactions that result in clean release of the corresponding alcohols. This was demonstrated for a variety of protected primary, secondary and tertiary hydroxyl groups, including the 5xe2x80x2-hydroxy group of thymidine. Examples of sensitizers that are effective in promoting photolytic release include 9,10-dimethylanthracene and 9-methylcarbazole. GC/MS and NMR analysis of the by-products formed in these release reactions implicates the intermediacy of radical ion intermediates in these reactions. It is further demonstrated that the electron transfer sensitized release method can be extended to phosphate esters and di-functional acids.
In particular, the invention relates to a compound having the Formula: 
wherein
R1 is an aryl or heteroaryl group; and
X is one of OCO2R2 or OP(O)(OR3)2, wherein R2 and R3, each independently, are the residue of an alcohol containing compound (i.e. R2 or R3, together with the neighboring oxygen, when bound to hydrogen, is the alcohol).
The invention also relates to a compound having the Formula: 
wherein
R1 is an aryl or heteroaryl group,
n is 2-6, and
Z is the residue of any compound having two or more carboxyl groups.
The invention also relates to a method of preparing a protected compound having the Formula: 
wherein
R1 is an aryl or heteroaryl group; and
X is OCO2R2, wherein R2 is the residue of an alcohol containing compound, comprising condensing the chloroformate derivative of the alcohol with the compound having Formula: 
under conditions whereby said protected compound is produced.
The invention also relates to a method of preparing a protected compound having the Formula: 
wherein
R1 is an aryl or heteroaryl group; and
X is OCO2R2, wherein R2 is the residue of an alcohol containing compound, comprising reacting the alcohol with N,N-carbonyldiimidazole or phosgene, and then adding the compound having Formula: 
under conditions whereby said protected compound is produced.
The invention also relates to a method of preparing a protected compound having the Formula: 
wherein
R1 is an aryl or heteroaryl group; and
X is OCO2R2, wherein R2 is the residue of an alcohol containing compound, comprising reacting methyl triflate together with N,N-carbonyldiimidazole, then adding the alcohol, and then adding the compound having Formula: 
under conditions whereby said protected compound is produced.
The invention also relates to a method of preparing a protected compound having the Formula: 
wherein
R1 is an aryl or heteroaryl group; and
X is OP(O)(OR3)2, wherein R3 is the residue of an alcohol containing compound, comprising reacting the compound having Formula: 
with a compound having the Formula: 
under conditions whereby said protected compound is produced.
The invention also relates to a method of preparing a protected compound having Formula: 
wherein
R1 is an aryl or heteroaryl group,
n is 2-6, and
Z is the residue of a compound having two or more carboxyl groups; comprising reacting the compound having Formula: 
with a compound having Formula: 
under conditions whereby said protected compound is produced.
The invention also relates to a method of deprotecting a compound having the Formula: 
wherein
R1 is an aryl or heteroaryl group; and
X is OCO2R2, wherein R2 is the residue of an alcohol containing compound, comprising irradiating said compound in the presence of a sensitizer under conditions whereby said compound is deprotected and the alcohol containing compound is produced.
The invention also relates to a method of deprotecting a compound having the Formula: 
wherein
R1 is an aryl or heteroaryl group; and
X is OP(O)(OR3)2, wherein R3 is the residue of an alcohol containing compound, comprising irradiating said compound in the presence of a sensitizer under conditions whereby said compound is deprotected and the alcohol containing compound is produced.
The invention also relates to a method of deprotecting a compound having Formula: 
wherein
R1 is an aryl or heteroaryl group,
n is 2-6, and
Z is the residue of a compound having two or more carboxyl groups; comprising irradiating said compound in the presence of a sensitizer under conditions whereby said compound is deprotected and the alcohol containing compound is produced.